Helicobacter pylori, a human specific gastric pathogen, colonizes the human gastric mucosa and the consequence is a higher prevalence of gastric diseases, such as chronic active gastritis and peptic ulcer disease. In the industrialized world, less than 20% of young people are infected, increasing to about half the population by 50 years of age. H. pylori has adapted to the hostile and acidic environment of the human stomach. Peristalsis and the high turnover rate of mucus and epithelial cells pose serious obstacles for microbes that strive to retain a niche in the gastric epithelial lining. Here, H. pylori can establish a protected niche for survival and long-term colonization of the gastric mucosa. Once established in the host, the bacteria can persist for the lifetime of the host. Chronic infection has been correlated to the development of gastric adenocarcinoma, one of the most common forms of cancer in humans (reviewed in Cover et al, 2001). Interestingly, most infected individuals show no clinical symptoms, implying the influence of additional factors in the pathogenesis of the disease such as diet, genetic predisposition, age of acquisition of the infection, and the genotype of the infecting strain.
H. pylori colonizes the human gastric mucosa by adherence both to the mucous epithelial cells and to the mucus layer lining the gastric epithelium. H. pylori demonstrates various adhesion properties for adherence to the mucus layer and the epithelial cell glycoproteins and glycolipids. The microbial affinity for specific receptor structures, in combination with unique tissue-specific distribution of receptors, will restrict the colonization to the gastric/duodenal mucosa. The H. pylori adherence to the fucosylated blood group antigens Lewis b and H-1, (described by Clausen, et al, 1989) in human gastric mucosa has been demonstrated (Boŕen, et al, 1993). Recently the cognate H. pylori blood group antigen binding adhesin, BabA, was identified (Ilver, et al., 1998). A panel of 95, clinical isolates was analyzed for Lewis b antigen binding properties. The majority of the isolates, 66%, were found positive for binding, demonstrating the high prevalence of blood group antigen binding activity among clinical isolates (Ilver, et al., 1998). By epidemiological screening, the Lewis b antigen binding property was found prevalent among the virulent strains that carry the cagPathogenicity Island and the vacuolating cytotoxin, i.e. the triple-positive strains. It is therefore proposed that Lewis b antigen mediated adherence of H. pylori play a critical role for development of severe gastric disease (Gerhard, et al., 1999).
The International Patent Application No. PCTVSE97/01009, published as WO97/47646, relates to the Heliobacter pylori adhesin binding group antigen.
An investigation of the influence of oral H. pylori on the success of eradication therapy suggests that the presence of oral H. pylori is an important factor for gastric infection (due to the numbers of patients who proved to be recurrent or refractory after eradication therapy). The most plausible explanation would be that these patients were infected with H. pylori in the oral cavity and dental plaques (Miyabayashli, et al, 2000), which suggests that H. pylori infections should be eradicated.
From U.S. Pat. No. 5,633,244, it is known to treat gastritis and peptic ulcer caused by H. pylori by administration of an acid degradable antibacterial compound in combination with a histamine-H2 receptor blocking compound. The acid degradable antibacterial compound can also be used in combination with a proton pump inhibitor such as omeprazole and lansoprazole (U.S. Pat. No. 5,629,305). The antibacterial compound is a penicillin, such as benzylpenicillin, or a macrolide, such as erythromycin.
The increased antibiotic resistance among virulent bacterial strains is a major cause for the development of alternative anti-microbial strategies, such as functional food strategies. Detailed knowledge about the mechanisms which support the adherence processes of H. pylori is vital for the development of alternative anti-microbial strategies, such as the invention described and claimed for in the present pending application.